Key information relevant to the recruitment process for the
overall study, such as dates of the recruitment period and locations

The study was conducted at 5 international sites – Ghana, Kenya, Mali, Bangladesh, and Vietnam from 29 March 2007 (first patient in) to 13 October 2008 (last dose given).

Last subject completed follow-up: 31 March 2009

All data corrections applied (Frozen File): 20 July 2009

Pre-Assignment Details

Significant events and approaches for the overall study
following participant enrollment, but prior to group assignment

Excluded from the trial before assignment to groups were subjects: with history of active gastrointestinal illness (vomiting, diarrhea, elevated temperature); who were participating in (or expected to participate in) other investigational-product studies; who could not be followed adequately for safety.

Reporting Groups

Description

RotaTeq™ - Africa

Three doses of RotaTeq™ (Rotavirus vaccine, live, oral, pentavalent) administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination, and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study.

Placebo - Africa

Three doses of Placebo matching RotaTeq™ administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study.

RotaTeq™ - Asia

Three doses of RotaTeq™ (Rotavirus vaccine, live, oral, pentavalent) administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination, and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study.

Placebo - Asia

Three doses of Placebo matching RotaTeq™ administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study.

Participant Flow: Overall Study

RotaTeq™ - Africa

Placebo - Africa

RotaTeq™ - Asia

Placebo - Asia

STARTED

2733
[1]

2735
[1]

1018
[1]

1018
[1]

Vaccinated at Visit 1

2733

2735

1018

1018

Vaccinated at Visit 2

2657

2666

1013

1009

Vaccinated at Visit 3

2613

2612

1009

1007

COMPLETED

2607
[2]

2601
[2]

1009
[2]

1007
[2]

NOT COMPLETED

126

134

9

11

Adverse Event

12

21

1

0

Lost to Follow-up

62

69

4

3

Protocol Violation

4

2

2

2

Withdrawal by Subject

48

42

2

6

[1]

Subjects who passed all entry criteria and who were randomized in to the study

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

No text entered.

Reporting Groups

Description

RotaTeq™ - Africa

Three doses of RotaTeq™ (Rotavirus vaccine, live, oral, pentavalent) administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination, and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study.

Placebo - Africa

Three doses of Placebo matching RotaTeq™ administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study.

RotaTeq™ - Asia

Three doses of RotaTeq™ (Rotavirus vaccine, live, oral, pentavalent) administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination, and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study.

Placebo - Asia

Three doses of Placebo matching RotaTeq™ administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study.

Occurrence of Severe Clinical Rotavirus Disease Caused by Any Rotavirus Serotype More Than 14 Days Following the Third Dose [ Time Frame: At least 14 days following the third vaccination ]

Measure Type

Primary

Measure Title

Occurrence of Severe Clinical Rotavirus Disease Caused by Any Rotavirus Serotype More Than 14 Days Following the Third Dose

Measure Description

No text entered.

Time Frame

At least 14 days following the third vaccination

Safety Issue

No

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

Per Protocol Population

Reporting Groups

Description

RotaTeq™ - Africa

Three doses of RotaTeq™ (Rotavirus vaccine, live, oral, pentavalent) administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination, and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study.

Placebo - Africa

Three doses of Placebo matching RotaTeq™ administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study.

RotaTeq™ - Asia

Three doses of RotaTeq™ (Rotavirus vaccine, live, oral, pentavalent) administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination, and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study.

Placebo - Asia

Three doses of Placebo matching RotaTeq™ administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study.

Measured Values

RotaTeq™ - Africa

Placebo - Africa

RotaTeq™ - Asia

Placebo - Asia

Number of Participants Analyzed
[units: participants]

2357

2348

991

978

Occurrence of Severe Clinical Rotavirus Disease Caused by Any Rotavirus Serotype More Than 14 Days Following the Third Dose
[units: Subjects]

Subjects with rotavirus gastroenteritis cases

79

129

38

71

Subjects without rotavirus gastroenteritis cases

2278

2219

953

907

Statistical Analysis 1 for Occurrence of Severe Clinical Rotavirus Disease Caused by Any Rotavirus Serotype More Than 14 Days Following the Third Dose

Groups [1]

RotaTeq™ - Africa vs. Placebo - Africa

Method [2]

Exact binomial test

P Value [3]

<0.001

Efficacy = 1-Relative Risk [4]

39.3

95% Confidence Interval

( 19.1 to 54.7 )

[1]

Additional details about the analysis, such as null hypothesis and power calculation:

The number randomized is different from the number analyzed because some data were excluded from the analysis: subjects were classified as unevaluable due to wildtype rotavirus in stool before 14 days Postdose 3, incomplete clinical and/or laboratory results, or stool samples collected out of day range. Rotavirus gastroenteritis cases are subjects with one or more positive episodes. The most severe positive episode is used for the date of the case.

[2]

Other relevant method information, such as adjustments or degrees of freedom:

No text entered.

[3]

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

Efficacy>0%. Based on p< 1/(1+k), where p is proportion of subjects with outcome in vaccine group relative to total number of subjects with outcome, and k is ratio of follow-up time; placebo / vaccine. Based on conditional binomial approach.

[4]

Other relevant estimation information:

Efficacy = 1-RR, expressed as a percentage; the RR is the incidence in the vaccine group / the incidence in the placebo group.

Statistical Analysis 2 for Occurrence of Severe Clinical Rotavirus Disease Caused by Any Rotavirus Serotype More Than 14 Days Following the Third Dose

Groups [1]

RotaTeq™ - Asia vs. Placebo - Asia

Method [2]

Exact binomial test

P Value [3]

<0.001

Efficacy = 1-Relative Risk [4]

48.3

95% Confidence Interval

( 22.3 to 66.1 )

[1]

Additional details about the analysis, such as null hypothesis and power calculation:

The number randomized is different from the number analyzed because some data were excluded from the analysis: subjects were classified as unevaluable due to wildtype rotavirus in stool before 14 days Postdose 3, incomplete clinical and/or laboratory results, or stool samples collected out of day range. Rotavirus gastroenteritis cases are subjects with one or more positive episodes. The most severe positive episode is used for the date of the case.

[2]

Other relevant method information, such as adjustments or degrees of freedom:

No text entered.

[3]

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

Efficacy>0%. Based on p< 1/(1+k), where p is proportion of subjects with outcome in vaccine group relative to total number of subjects with outcome, and k is ratio of follow-up time; placebo / vaccine. Based on conditional binomial approach.

[4]

Other relevant estimation information:

Efficacy = 1-RR, expressed as a percentage; the RR is the incidence in the vaccine group / the incidence in the placebo group.

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

Per Protocol Population

*N analyzed for Serotype P1A[8] is 188

Reporting Groups

Description

RotaTeq™ - Africa

Three doses of RotaTeq™ (Rotavirus vaccine, live, oral, pentavalent) administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination, and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study.

Placebo - Africa

Three doses of Placebo matching RotaTeq™ administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study.

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

Per Protocol Population

Reporting Groups

Description

RotaTeq™ - Asia

Three doses of RotaTeq™ (Rotavirus vaccine, live, oral, pentavalent) administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination, and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study.

Placebo - Asia

Three doses of Placebo matching RotaTeq™ administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study.